Prostaglandins (PG) and cyclic nucleotides appear to be important regulators of cell function and may therefore have a central role in modulation of disordered immune/inflammatory responses in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Subcutaneous administration of PGE1 prevents progression of disease and nephritis and markedly prolongs survival of NZB/W (lupus) mice. We will determine whether oral administration of a PGE1 analog is able to halt the progress of glomerulonephritis in lupus. The mechanisms whereby PGE compounds influence the course of murine lupus will be investigated. The effect of PGE therapy on and the roles of prostaglandins and cyclic nucleotides in macrophage function, suppressor activity, and lymphocyte maturation will be examined. The role of prostaglandins in the regulation of cell-cell communication in the autologous mixed leucocyte reaction will be studied, since the proliferative response of lymphocytes from SLE patients is impaired in this in vitro system. PGE will be administered orally to human subjects and its effect on several functions of peripheral blood leucocytes will be studied. These will include proliferative responses and lymphokine production following exposure of lymphocytes to mitogens or nDNA, lymphocyte adherence to virus infected cells, and lysosomal enzyme release from phagocytic cells.